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52. Testing for pathway (in)activation by using Gaussian graphical models

Author

van Wieringen, Wessel N., Peeters, Carel F.W., de Menezes, Renee X., van de Wiel, Mark A., van Wieringen, Wessel N., Peeters, Carel F.W., de Menezes, Renee X., and van de Wiel, Mark A.

Abstract

Genes work together in sets known as pathways to contribute to cellular processes, such as apoptosis and cell proliferation. Pathway activation, or inactivation, may be reflected in varying partial correlations between the levels of expression of the genes that constitute the pathway. Here we present a method to identify pathway activation status from two-sample studies. By modelling the levels of expression in each group by using a Gaussian graphical model, their partial correlations are proportional, differing by a common multiplier that reflects the activation status. We estimate model parameters by means of penalized maximum likelihood and evaluate the estimation procedure performance in a simulation study. A permutation scheme to test for pathway activation status is proposed. A reanalysis of publicly available data on the hedgehog pathway in normal and cancer prostate tissue shows its activation in the disease group: an indication that this pathway is involved in oncogenesis. Extensive diagnostics employed in the reanalysis complete the methodology proposed.

Published
2018
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53. [P3-226]: PROFILING PERIPHERAL METABOLIC DYSREGULATION IN ALZHEIMER's DISEASE: THE ADDED VALUE OF MULTIPLE SIGNATURES

Author

de Leeuw, Francisca A., primary, Peeters, Carel F.W., additional, Kester, Maartje I., additional, Harms, Amy C., additional, Hankemeier, Thomas, additional, Struys, Eduard A., additional, Demirkan, Ayşe, additional, Scheltens, Philip, additional, van Vlijmen, Herman W.T., additional, van de Wiel, Mark A., additional, van Duijn, Cornelia M., additional, van der Flier, Wiesje M., additional, and Teunissen, Charlotte E., additional

Published
2017
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